A review of the virological efficacy of the 4 World Health Organization-recommended tenofovir-containing regimens for initial HIV therapy

Abstract

We systematically reviewed studies of the virological efficacy of the 4 new tenofovir (TDF)-containing regimens recommended for initial antiretroviral (ARV) therapy in the 2010 World Health Organization ARV Treatment Guidelines. Thirty-three studies assessed the efficacy of 1 or more TDF-containing regimens: TDF/lamivudine (3TC)/nevirapine (NVP) (n = 3), TDF/ emtricitabine (FTC)/NVP (n = 9), TDF/3TC/efavirenz (EFV) (n = 6), and TDF/FTC/EFV (n = 19). TDF/3TC/NVP was the least well-studied and appeared the least efficacious of the 4 regimens. In 2 comparative studies, TDF/3TC/NVP was associated with significantly more virological failure than AZT/3TC/NVP; a third study was terminated prematurely because of early virological failure. TDF/FTC/NVP was either equivalent or inferior to its comparator arms. TDF/3TC/EFV was equivalent to its comparator arms. TDF/FTC/EFV was equivalent or superior to its comparator arms. Possible explanations for these findings include the greater antiviral activity of EFV versus NVP and longer intracellular half-life of FTC-triphosphate versus 3TC-triphosphate. Further study of TDF/3TC/NVP is required before it is widely deployed for initial ARV therapy.

Figure 1.

Summary of search results. A, Search results from online journal and trial databases; B, search results from conference abstracts. A description of the online databases and conferences can be found in the Supplementary Material. Definitions: “Duplicate publication”: Multiple publications arising from the same study or patient cohort. “No virologic outcome”: No virologic endpoints were available in the publication or abstract. “Regimen or unclear or did not include regimen of interest”: Incomplete description of which antiretroviral (ARV) regimens were used, or failure to correlate specific ARV regimens with virologic data. “Rx experienced or simplification”: Study subjects were either (1) treatment experienced, (2) included a mix of treatment naive and treatment experienced patients, or (3) virologically suppressed at baseline and received a tenofovir (TDF)-regimen as simplification. “Sample size”: Study included 10 or fewer patients. “Non-English”: Study was only published in a foreign language.

Figure 2.

Relative risk (RR) and 95% confidence interval (CI) for treatment and virological failure in comparative studies: RR and 95% CI for studies comparing TDF/3TC/NVP, TDF/FTC/NVP, TDF/3TC/EFV, and TDF/FTC/EFV to another regimen are depicted. Regimens containing non-US Food and Drug Administration-approved antiretrovirals (ARVs) or ARV combinations are not shown. RR for prospective studies are depicted as black points, and RR for retrospective studies are depicted as gray points. Points to the left of midline represent improved virological efficacy for the tenofovir (TDF)-containing regimen. Points to the right of midline represent improved virological efficacy for the comparator regimen. Abbreviations: AZT, zidovudine; 3TC, lamivudine; ABC, abacavir; ATV/r, boosted atazanavir; ddI, didanosine; EFV, efavirenz; FTC, emtricitabine; LPV/r, boosted lopinavir; NVP, nevirapine; NVP XR, extended-release nevirapine; RAL, raltegravir; RPV, rilpivirine; TDF, tenofovir.